An Update of the Evidence
for the United States Preventive Services Task Force (continued)
Discussion
Carotid
artery stenosis is 1 of several etiologic factors for stroke, an important
health problem with a high burden of disease in the United States. It is
important to consider the possibility that screening asymptomatic people with ultrasonography
to detect clinically important CAS for the purpose of performing carotid
endarterectomy may reduce the large burden of suffering due to stroke. Although
the percentage of all strokes that could potentially be reduced by screening
for CAS is relatively small, this is a large number of strokes when considered
across the United States.
The
magnitude of contribution of CAS to the morbidity and mortality associated with
stroke is not well characterized, nor is the natural progression of CAS. We
estimate the prevalence of CAS 60% to 99% in the general population older than 65
years to be about 1%. Carotid artery stenosis is more prevalent in older
adults, smokers, persons with hypertension, and persons with heart disease.
Unfortunately, research has found no single risk factor or clinically useful
risk stratification tool that can reliably and accurately distinguish people
who have clinically important CAS from people who do not.
Duplex
ultrasonography is a noninvasive screening test. Its reported accuracy is
approximately 94% sensitive and 92% specific for CAS of 60% to 99%. In a
low-prevalence population, the number of false-positive test results is high.
In the case of screening for CAS, false-positive results are important. If all
positive tests are followed by cerebral angiography, about 1% of people will experience
a nonfatal stroke as a result of the angiography. If positive test results are
not followed by confirmatory angiography but rather by MRA or CTA—tests that
are less than 100% accurate—some people will have unnecessary carotid
endarterectomy. Carotid endarterectomy is associated with important
complications, including a perioperative stroke or death rate of 2.4% to 3.7%; therefore,
some people will be harmed unnecessarily.
Under
carefully controlled conditions, treatment with carotid endarterectomy for
asymptomatic CAS can result in a net absolute reduction in stroke rates—approximately
5% over 5 to 6 years (about 2.5% absolute risk reduction for disabling
strokes). This benefit has been shown in selected patients with selected
surgeons, and it must be weighed against a small increase in nonfatal myocardial
infarctions. The net benefit for carotid endarterectomy largely depends on
people surviving the perioperative period without complications. The 2 RCTs
that found a benefit to surgery over medical management had 30-day
perioperative rates of stroke and death of 2.7% to 2.8%. In large observational
studies using administrative databases, the average complication rates ranged
from 1.6% to 3.7%; statewide rates varied greatly by state, ranging from 2.3%
to 6.7%.
Other
issues prevent the determination of a good estimate of benefit from CAS
screening in the general primary care setting. First, the patients and surgeons
in the RCTs of carotid endarterectomy treatment were highly selected, and the patients
had high stroke risk. Second, the absolute benefit of screening and carotid
endarterectomy treatment depends on a low perioperative rate of stroke or
death. A small increase in perioperative strokes or death could counteract the
benefits. There is no validated strategy for reliably identifying patients that
are at high enough risk for stroke to benefit from carotid endarterectomy but at
low enough risk for perioperative complications. Third, the beneficial outcome
of decreased strokes in the RCTs does not account for additional harms of carotid
endarterectomy, including nonfatal myocardial infarction. In addition, the
absolute risk reduction in the carotid endarterectomy trials is relatively
small (4 to 6 percentage points over 6 years in ACST).
Another
important limitation of the evidence on the benefit of treatment with carotid
endarterectomy is that the medical treatment arm in the RCTs was poorly defined
and probably did not include intensive blood pressure and lipid control, as is
standard practice today. It is difficult to determine what effect current
standard medical therapy would have on overall benefit from carotid
endarterectomy. The use of current medical therapy could have reduced the
stroke rate in the medical treatment arm of these trials, thus probably reducing
the overall benefit to treatment with carotid endarterectomy.
Another
issue regarding the evidence on carotid endarterectomy is the timing of strokes
and perioperative death. The events in the carotid endarterectomy arm of the
RCTs occurred earlier than those in the medical management arm. The Kaplan−Meier
curves in ACST cross from net harm to net benefit at about 1.5 years after carotid
endarterectomy for men, and at nearly 3 years after carotid endarterectomy for
women.49-53 The estimated survival from these curves beyond the actual
follow-up time may not be applicable. It is possible that the benefit of carotid
endarterectomy will be limited to a specific period and will not continue
unabated into the future, as projected in the trials. Thus, the actual (not
projected) risk reduction for carotid endarterectomy over 5 to 10 years is
still uncertain. The evidence would suggest that the absolute benefit of
screening and carotid endarterectomy in people with asymptomatic CAS in the
general population is small.
Table 2 shows
hypothetical outcomes of a screening program for asymptomatic CAS. These
calculations are based on many assumptions that may limit the widespread
applicability to certain populations. These assumptions include that ultrasonography
is used as the initial screening test with a sensitivity of 0.94 and
specificity of 0.92, the prevalence in general primary care population older
than 65 years is 1%, all patients with a positive test result go to surgery, and
the event rate with carotid endarterectomy (perioperative stroke or death) is
3.1%. Table 2 shows further detail on assumptions. According to these
calculations, the best tradeoff between benefits and harms comes from a
strategy of carotid duplex ultrasonography screening followed by MRA
confirmation. Given this strategy, about 23 strokes would be prevented over 5
years by screening 100,000 people with a true prevalence of clinically
important CAS of 1%. Thus, about 4348 people need to undergo screening to
prevent 1 stroke (number needed to screen) after 5 years. Double this number
(8696 persons) would need to be screened to prevent 1 disabling stroke. If a
higher-risk population with an actual prevalence of 5% could be defined in whom
the screening and confirmation strategy defined above was used, about 217
strokes would be prevented over 5 years by screening 100 000 people. This
translates into a number needed to screen of about 461 to prevent 1 stroke over
5 years, or a number needed to screen of 922 to prevent 1 disabling stroke over
5 years. An additional 34 people would have nonfatal myocardial infarction as a
result of screening. However, risk assessment tools that accurately identify
persons at high risk for a stroke from CAS are not available, and therefore it
is not possible to identify people from a high-risk group with a prevalence of
5% who might benefit from screening and treatment with carotid endarterectomy.
Asymptomatic
CAS probably contributes relatively little to the overall stroke burden.
Although we did not review the evidence on medical treatment, there are
accepted medical strategies to prevent stroke. Until we address the gaps in the
evidence that screening and treatment with carotid endarterectomy provides
overall benefits to the general population, clinicians' efforts might be more
practically focused on optimizing medical management.
Emerging
Issue: Stenting for CAS
The
use of carotid artery angioplasty with stenting for CAS has increased in recent
years. This technology has emerged as a potential alternative to carotid
endarterectomy for patients who are not candidates for carotid endarterectomy
because of high-risk comorbid conditions.
A
Cochrane systematic review of 5 RCTs of stenting versus carotid endarterectomy
for symptomatic and asymptomatic patients at high risk for complications from carotid
endarterectomy found no difference in 30-day or 1-year outcomes between
treatment groups.54 No study has randomly allocated asymptomatic patients
similar to those in the ACAS or ACST trials to stenting versus carotid
endarterectomy, and no trial has reported results beyond 1 year. The largest
study that reported the most positive results showed a nonstatistically
significant trend toward a reduction in perioperative stroke, death, and nonfatal
myocardial infarction.55 This study, however, was terminated early because
of slow recruitment. Thus, we cannot determine whether the benefits of stenting
differ from those of carotid endarterectomy.
Research Gaps
High-quality
studies of the true prevalence (rather than the ultrasonography-based
prevalence) of clinically important CAS in usual primary care populations are
needed. Other research gaps include 1) evidence for a validated, reliable risk
stratification tool that would allow us to distinguish those people who might
benefit from screening from those who would more likely be harmed, 2) evidence
on improved screening strategies that do not generate many false-positive results
and unnecessary harms, and 3) further studies on confirmatory strategies that
do not lead to additional harms.
Return to Contents
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Notes
Current Author Addresses
a. Drs. Wolff and Miller: Center for Primary Care, Prevention,
and Clinical Partnerships, Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850.
b. Dr. Guirguis-Blake: Tacoma Family Medicine Residency, Department
of Family Medicine, University of Washington, 521 Martin Luther King Jr. Way, Tacoma,
WA 98405.
c. Dr. Gillespie: School of Medicine, University of North
Carolina, CB #7075, 6th Floor, Burnett-Womack Building, 099 Manning Drive, Chapel
Hill, NC 27599.
d.
Dr. Harris: School of Medicine, University of North Carolina, CB #7590. Sheps Center, 725 Martin Luther King Jr. Boulevard, Chapel Hill, NC 27599-7590.
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investigators have any affiliations or financial involvement (e.g., employment,
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Source: U.S. Preventive Services Task Force. Screening for carotid artery stenosis: an update of the evidence for the United States Preventive Services Task Force. Annals of Internal Medicine 2007;147: 860-70.
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AHRQ Publication No. 08-05102-EF-4
Current as of December 2007
Internet Citation:
U.S. Preventive Services Task Force. Screening For Carotid Artery Stenosis: An Update of the Evidence for the United States Preventive Services Task Force. AHRQ Publication No. 08-05102-EF-4, December 2007. First published in Annals of Internal Medicine 2007;147: 860-70. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstf07/cas/casarticle.htm
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